PNLDC1

Chr 6AR

PARN like ribonuclease domain containing exonuclease 1

Also known as: HsPNLDC1, SPGF57, Trimmer

NCBI Gene: 154197ENSG00000146453UniProt: Q8NA58

Enables poly(A)-specific ribonuclease activity. Involved in nuclear-transcribed mRNA poly(A) tail shortening; piRNA processing; and spermatogenesis. Located in endoplasmic reticulum. Implicated in spermatogenic failure 57. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Spermatogenic failure 57MIM #619528
AR
103
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PNLDC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 61 VUS of 103 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.98LOEUF
pLI 0.000
Z-score 1.63
OE 0.71 (0.53–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.80Z-score
OE missense 0.87 (0.79–0.96)
261 obs / 299.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.53–0.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.79–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 27 / 37.8Missense obs/exp: 261 / 299.9Syn Z: -1.15

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic5
VUS61
Likely Benign9
28
Pathogenic
5
Likely Pathogenic
61
VUS
9
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
23
0
28
Likely Pathogenic
2
2
1
0
5
VUS
0
55
6
0
61
Likely Benign
0
7
0
2
9
Benign
0
0
0
0
0
Total566302103

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PNLDC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spermatogenic failure 57

MIM #619528

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variant PNLDC1, Defective piRNA Processing, and Azoospermia.
Nagirnaja L et al.·N Engl J Med
2021
How genetic defects in piRNA trimming contribute to male infertility.
Mann JM et al.·Andrology
2023Review
A novel loss-of-function variant in PNLDC1 inducing oligo-astheno-teratozoospermia and male infertility.
Zhao SY et al.·Asian J Androl
2023Case report
A novel missense variant in PNLDC1 associated with nonobstructive azoospermia.
Rahimian M et al.·J Genet
2024
A balanced translocation disrupting BCL2L10 and PNLDC1 segregates with affective psychosis.
Bouwkamp CG et al.·Am J Med Genet B Neuropsychiatr Genet
2017Case report
The role of homozygous LOF variant of the PNLDC1 gene in oligo-astheno-teratozoospermia (OAT) and male infertility.
Cheng ZX et al.·Asian J Androl
2023
Diagnostic yield of exome sequencing in nonobstructive azoospermia (NOA): A systematic review and meta-analysis.
Zhou F et al.·PLoS One
2025Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools